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Published OnlineFirst April 7, 2013; DOI: 10.1158/2326-6066.CIR-13-0017

Cancer Editorial Immunology Research

A Message from the Founding Editor-in-Chief

Glenn Dranoff, MD Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

This is an auspicious time for the AACR to launch Cancer overcome are: (i) a lack of clarity regarding the logic of how Immunology Research, a new journal devoted to cancer immune responses work; (ii) the large number of soluble immunology and immunotherapy. Recent clinical investiga- factors, surface molecules, and cell populations in the immune tions have convincingly established that the immune system system that seem to be steadily increasing; (iii) a limited can be triggered to accomplish meaningful tumor destruction. background in the relevant history and current literature of The administration of blocking monoclonal antibodies against the field; (iv) a lack of familiarity with many immunologic the negative immune checkpoints, cytotoxic T lymphocyte- techniques; (v) and uncertainty regarding how to prioritize associated antigen 4 (CTLA-4) and programmed death-1 particular areas of host–tumor cell interactions for more (PD-1), elicits remarkable antitumor effects in some patients detailed exploration. with otherwise refractory disease. Moreover, cancer vaccines, Cancer Immunology Research will address this important adoptive therapy with engineered T cells, and other immuno- challenge through playing a leading role in educating the modulatory antibodies are similarly showing promising anti- greater cancer research community regarding the principles tumor activity. Collectively, these exciting results indicate and opportunities in cancer immunology. A major benefitof that immunologic manipulations are likely to become a central this investment will be to catalyze cross-disciplinary investiga- component of cancer treatment. tions, which might dramatically accelerate progress toward a In parallel to these advances in therapeutics, substantive deeper understanding of the host–tumor relationship, more progress in elucidating the mechanisms involved in endoge- potent therapeutics, and improved clinical outcomes. Indeed, nous host antitumor responses has delineated a key role for cancer immunology is currently reaping the benefits of basic immunity in cancer pathogenesis. The principles of immuno- and translational studies in allied disciplines of immunology, editing have now been revealed not only in models typi- such as autoimmunity, infectious disease, transplantation, and cally used by cancer immunologists, but also in genetically immunodeficiency; insights from these fields are now regularly engineered oncogene-driven systems that are a mainstay of being applied to the problems of tumor immunity. investigations in cancer biology. In addition, the pivotal con- To accomplish this educational mission, Cancer Immunology tribution of persistent inflammation to promoting tumor Research has developed several special features. The first is initiation and progression has now been broadly recognized, "Masters of Immunology," a series of primers on the funda- highlighting the dual roles of immunity in tumor development. mentals of immunology, particularly as they relate to cancer. Notwithstanding these important examples of how immu- These short pieces will be drafted by leading scholars who will nology is entering the mainstream of cancer science, many present basic immunologic concepts in an accessible format cancer researchers have difficulty accessing the discipline and that includes informative graphics. A broad spectrum of topics recognizing opportunities for productive new research direc- will be covered in the fullness of time, and the cycle will be tions. There are many factors that contribute to this perception repeated (in several iterations), allowing individual areas to be of a high barrier to entry. Among the hurdles that need to be presented in increasingly greater detail and with a richer perspective on how a particular subject fits into the overall schema of tumor immunity. These primers will be organized into a virtual cancer immunology textbook on the journal doi: 10.1158/2326-6066.CIR-13-0017 website. Continuing medical education credits will also be Ó2013 American Association for Cancer Research. offered for studying these primers, which should be of practical

2 Cancer Immunol Res; 1(1) July 2013

Cancer Immunology Research Overview

interest to clinicians who desire a deeper knowledge of immu- and Mark Selby and colleagues establish the critical impor- nology. For this inaugural issue, Hidde Ploegh has drafted an tance of antibody isotype to the therapeutic activity of CTLA- illuminating and eloquent introductory essay entitled "The 4 blocking antibodies in murine models. These investigators Logic of the Immune System." This piece will serve as an enticing reveal the ability of anti-CTLA-4 monoclonal antibodies to entry point to the mysteries and intricacies of immunity. trigger a striking reduction in intratumoral, but not peri- þ To complement these primers, Cancer Immunology Research pheral, FoxP3 regulatory T cells, likely through Fc receptor- will present "Cancer Immunology at the Crossroads," a series dependent cytotoxic mechanisms. These provocative find- that will be devoted to exploring compelling opportunities for ings uncover a new aspect of immune checkpoint blockade, cross-disciplinary research. Prominent investigators will outline with important implications for further therapeutic devel- in short pieces specific areas where cancer immunology over- opment and patient selection. In a second story, Daniel laps with other cancer research disciplines and suggest a few Powell and Evripidis Lanitis and colleagues detail an attrac- possibilities for fruitful collaboration. These features will high- tive strategy for improving the therapeutic index of chimeric light intersections not only with allied basic sciences such as antigen receptor-expressing T cells. By separating T-cell sig- genetics, cancer biology, metabolism, pathology, engineering, naling domains in 2 chimeric antigen receptors specific imaging, infectious disease, and population studies, but also for distinct targets, the investigators show that full T-cell areas relevant to translational and clinical development activation requires concurrent recognition of both targets. paths. Among these subjects will be potential synergies with This property may allow the use of chimeric antigen recep- targeted therapy, radiation treatment, cytotoxics, and anti- tors that target proteins expressed on both tumor cells and angiogenic approaches; clinical trial design considerations; normal tissues; as long as the second tumor target is not also opportunities for new technologies; regulatory issues; expressed on the same normal cells as the first, the require- immune-related patterns of tumor response; and specific ment for combinatorial recognition may focus T-cell clinical settings in which immunotherapy might be effec- responses preferentially against tumor cells. tively employed. To kickoff this inspiring series, Nir Haco- A third type of original article that Cancer Immunology hen, Edward F. Fritsch, Todd A. Carter, Eric S. Lander, and Research will feature is the "Cancer Immunology Miniature." Catherine J. Wu outline an intriguing approach to person- These contributions may report on early clinical data or alized cancer vaccinations based on next generation discovery-based studies that are not sufficiently developed sequencing of individual patient tumors. The initiation of for publication as full Research Articles, but have the potential clinical testing is eagerly anticipated. to make a significant impact in research areas and clinical To round out the didactic components, Cancer Immun- investigation or care. These pieces might include well-ana- ology Research will also include reviews of rapidly developing lyzed, provocative case reports. An outstanding example of areas in the discipline. These pieces will probe more deeply this work is the detailed patient study of Carl June and Marcela into topics of central importance to the field and should Maus and colleagues published in this inaugural issue. The be of great interest to both specialists and newcomers. For authors describe the evolution of an anaphylactic reaction in a the inaugural issue, Bridget Keenan, Elizabeth Jaffee, and subject treated with T cells expressing a chimeric antigen Todd Armstrong have crafted a compelling summary of the receptor incorporating a mouse monoclonal antibody as the recent special AACR conference entitled "Tumor Immun- targeting moiety. Although this class of receptors has been ology: Multidisciplinary Science Driving Basic and Clinical safely administered to a growing number of patients, this Advances." This article offers an exemplary analysis of miniature sounds a cautionary note regarding antimurine ongoing work, highlighting the breadth and depth of investi- immune responses and suggests that the use of fully human gation in the field. constructs should be carefully considered. In addition to the educational mission, Cancer Immunology To advance the dual mission of Cancer Immunology Research will aspire to become the leading publication for Research in fostering education and original investigation, original work in cancer immunology. The journal will print Elizabeth Jaffee, Stanley Riddell, and Robert Vonderheide will outstanding articles reporting major advances in cancer serve as Deputy Editors. Each is a consummate physician- immunology, which may span the discipline from basic scientist who has successfully developed a novel therapeutic investigations in host–tumor interactions to developmental strategy from preclinical proof-of-concept experiments therapeutics in model systems, to early translational studies through early phases of testing in patients with cancer. This in patients, and late-stage clinical trials. These contri- rare experience coupled with a broad knowledge of the entire butions may be structured as either full Research Articles discipline positions the Deputy Editors as the ideal team to or Priority Briefs. Specific topics of interest include endog- oversee the didactic components of the journal. Their efforts enous antitumor immunity, tumor-promoting inflamma- should ensure the dissemination of knowledge of cancer tion, cancer antigens, vaccines, antibodies, cellular therapy, immunology to the larger cancer research community, there- cytokines, immune regulation, immune suppression, immuno- by stimulating new investigators to enter the field. modulatory effects of cancer treatment, emerging technologies, Nineteen distinguished scientists and physicians from and clinical investigations. around the globe will serve as the Senior Editors for Cancer Cancer Immunology Research is proud to showcase two Immunology Research. Their collective knowledge spans all of high-impact original articles in the inaugural issue, which are the major areas of cancer immunology and immunotherapy. both likely to advance the field significantly. Alan Korman TheSeniorEditorswilloverseereviewsoftheoriginalarticles,

www.aacrjournals.org Cancer Immunol Res; 1(1) July 2013 3

Editorial

assuring that they are conducted rigorously and timely; the and Michael Caligiuri for their vision and wisdom. We hope journal will maintain the highest levels of scholarship and that all of the efforts on behalf of Cancer Immunology Research intellectual rigor. A vibrant and accomplished Editorial Board will ensure that immunology, metaphorically and tangibly, will assist the Senior Editors in evaluating submitted manu- assumes a prominent position within the heart of cancer scripts. The broad participation of the cancer immunology research. community on the Editorial Board will assure that the journal helps generate new insights into the complex interplay between cancer and the immune system and accelerates the crafting of clinically efﬁcacious immunotherapies. The creation of Cancer Immunology Research reﬂects the many efforts of the skilled publications team at AACR, Glenn Dranoff, MD particularly Kelly Hadsell, Art Buchberg, and Diane Scott- Editor-in-Chief Lichter. Connie Gee also provided invaluable assistance in Cancer Immunology Research launching the journal. A special thanks to Drs. Margaret Foti Published OnlineFirst April 7, 2013.

4 Cancer Immunol Res; 1(1) July 2013 Cancer Immunology Research

A Message from the Founding Editor-in-Chief

Glenn Dranoff

Cancer Immunol Res 2013;1:2-4. Published OnlineFirst April 7, 2013.

Updated version Access the most recent version of this article at: doi:10.1158/2326-6066.CIR-13-0017

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